Defining The Characteristics And Treatment Options For XXYY Syndrome Print E-mail
Science - Genetics & Genome
Written by TS-Si News Service   
Wednesday, 27 August 2008 16:30
XXYY
TS-Si Genetics And
The Genome
Sacramento, CA, USA. Researchers are closer to understanding XXYY Syndrome, a rare genetic anomaly in which males have two "X" and two "Y" chromosomes. A research team conducted the largest study to date describing the medical and psychological characteristics of XXYY, developing recommendations for men and boys with the disorder.
 
The study of XXYY Syndrome illustrates the importance of developing a reliable observation baseline. Developmental biologists and geneticists study the underlying mechanisms that guide human development. A clear understanding of the consequences when events do not follow an expected pattern can provide important information on which to base prevention and/or treatment options.
 
A new look at XXYY syndrome: Medical and psychological features. Randi Hagerman, Nicole Tartaglia, Lindsey Albrecht, Ann Reynolds, Laura Fenton, Judith Ross, Jeannie Visootsak. American Journal of Medical Genetics Part A, 2008; 146a(12) 1509-1522. doi: 10.1002 / ajmg.a.32366
 
XXYY Syndrome (technically 48,XXYY) is a sex chromosome anomaly that is thought to occur in about one in 18,000-40,000 males in the general population. [N1] Boys with the syndrome usually come to the attention of physicians because of unique facial features, developmental delays, late puberty, skin ulcers, truncal obesity, and behavioral problems. 
 
Researchers at the UC Davis M.I.N.D. Institute and The Children's Hospital in Denver conducted the current study to identify the unique features of patients with XXYY for the purposes of informing the medical community and improving treatment approaches.
 
Randi Hagerman, medical director of the M.I.N.D. Institute and senior author of the study.
Randi Hagerman, medical director of the M.I.N.D. Institute and senior author of the study.
 
"We found that there are a variety of behaviors, learning disabilities and emotional problems that are unique to patients with XXYY syndrome that may be better addressed with more targeted therapies," Hagerman said  "Our research is important because it provides an accurate picture of what patients are experiencing that can help physicians who treat patients with the disorder."
 
"Until now, physicians have had to search the medical literature to patch together a treatment plan mostly based on information on Klinefelter syndrome," [N1] said Nicole Tartaglia, an assistant professor of pediatrics at the University of Colorado Denver School of Medicine. Tartaglia was a fellow at the M.I.N.D. Institute when the study was conducted.
 
As a result, people with XXYY weren't being screened for the specific medical problems associated with their disorder. They weren't receiving therapies or medications for the behavioral and neurodevelopmental issues that are more profound for them. And they weren't receiving the types of community services that can help them live independent lives. Our research is an important resource for families and practitioners."
 
For the current study, Tartaglia and Hagerman examined 95 males with XXYY syndrome between the ages of one and 55 years of age. Among their medical findings:
  • 19.4 percent had cardiac abnormalities such as congenital heart defects and mitral valve prolapse,
     
  • 87.6 percent had dental problems such as severe dental caries and malocclusion,
     
  • 15 percent had seizures and
     
  • 59.8 percent had asthma or other respiratory issues.
     
  • Intention tremor became more common with age and was present in 71 percent of study participants over 20 years old.
     
  • 45.7 percent who underwent brain MRIs showed abnormal white matter that may explain some learning difficulties.
Psychologically, the researchers found that:
  • 72.2 percent had attention-deficit/hyperactivity disorder.
     
  • Up to 28.3 percent had autism spectrum disorders.
In the previous literature, mental retardation was the norm. This study, however, found that:
  • 29.1 percent had IQ scores within the mental retardation range.
     
  • Learning disabilities were the more common cognitive impairments, affecting 70.9 percent of study participants.
"Life skills are more of a struggle for these males, and they may need different medications, a broader array of behavioral therapies and more intensive community support than those with Klinefelter syndrome," Tartaglia said.
 
The impetus to develop a complete description of the syndrome was driven by the parents' frustration over a lack of information. For years, parents of boys with XXYY Syndrome supported each other over the Internet, sharing stories of heartbreak and frustration. While their sons suffered everything from heart defects to learning disabilities, they could only point doctors and teachers to a 1960s scientific paper that first identified the condition along with a few outdated notes on its outcomes.
 
"We knew we needed a more complete description," said Renee Beauregard, of Aurora, Col., whose 26-year-old son, Kyle, was diagnosed with XXYY Syndrome at age 10. "We were tired of having our families running around the country looking for answers from people who didn't have them," said Beauregard, who is also a co-author on the study.
 
In 2003, Beauregard and other parents turned their frustration into advocacy and established the XXYY Project to support families. "The more we talked, the more we realized our boys had things in common that were not addressed in the literature," said Beauregard, the project's director. "We had to do something."
 
The parents had their children take part in the study, and they flew Tartaglia to the United Kingdom so that she could include XXYY boys living there in the research as well.
 
Now, with more concrete answers, parents like Beauregard and children like Kyle can find some peace of mind. "Kyle knows that people don't understand XXYY and therefore don't understand him as a person, she said. "The study helps the world know why he is like he is. It validates what he knows about himself and what we know about him. When he can't follow directions, it's not because he's stupid."
 


[N1] XXYY Syndrome has traditionally been classified as a variant of Klinefelter syndrome, in which males have one extra X chromosome (XXY). While the two disorders have some similarities, there is an emerging consensus among clinicians that two anomalies have significant differences.

[N2] Funding for the study was provided by the Bonfils-Stanton Foundation, UC Davis M.I.N.D. Institute, The XXYY Project and a Loan Repayment Program grant to Nicole Tartaglia from the National Institutes of Health (NIH).

 


A new look at XXYY syndrome: Medical and psychological features. Randi Hagerman, Nicole Tartaglia, Lindsey Albrecht, Ann Reynolds, Laura Fenton, Judith Ross, Jeannie Visootsak. American Journal of Medical Genetics Part A, 2008; 146a(12) 1509-1522. doi: 10.1002 / ajmg.a.32366

Abstract

XXYY syndrome occurs in approximately 1:18,000-1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multi-center study of 95 males age 1-55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall. Recommendations for evaluation and treatment are summarized.

 
XXYY syndrome, Klinefelter syndrome, sex chromosome abnormality, autism spectrum disorder, tremor, ADHD
 
TS-Si News ServiceThe TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.
 
Comments (0)Add Comment
feedSubscribe to this comment's feed
min/maxShow/Hide comments

Write comment
feedShow/Hide comment form

security code
Write the displayed characters


busy
< Prev   Next >
Last Updated on Wednesday, 27 August 2008 16:45